Comprehensive analysis of cuproptosis-related genes in immune infiltration and prognosis in lung adenocarcinoma.

Copper-dependent cell death, called cuproptosis, is connected to tumor development, prognosis, and the immune response. Nevertheless, the function of cuproptosis-related genes (CRGs) in the tumor microenvironment (TME) of lung adenocarcinoma (LUAD) remains unknown. This work used R software packages to classify the raw data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases of LUAD patients. Afterward, the connections of the various subgroups, clinical pathological traits, and immune infiltration (IMIF) features with the TME mutation status were explored. Ultimately, a nomogram and calibration curve were developed, aiming at enhancing the clinical application of CRG scores and estimating the survival probability of patients. Moreover, the relationships between cuproptosis and the molecular traits, immune cell infiltration of tumor tissue, prognosis, and clinical treatment of patients were investigated in this work. Subsequently, the CRG score was established to predict overall survival (OS), and its credible predictive ability in LUAD patients was identified. Afterward, a highly credible nomogram was created to contribute to the clinical viability of the CRG score. Furthermore, as demonstrated, gene signatures could be applied in assessing tumor immune cell infiltration, clinical traits, and prognosis. In addition, high tumor mutation burden, immunological activity, and significant survival probability were characterized by low CRG scores, and high CRG scores were related to immunosuppression and stromal pathway activation. The current work also discovered a predictive CRG-related signature for LUAD patients, probably contributing to TME trait clarification and more potent immunotherapy strategy exploration.

Resveratrol downregulates acute pulmonary thromboembolism-induced pulmonary artery hypertension via p38 mitogen-activated protein kinase and monocyte chemoattractant protein-1 signaling in rats.

AIMS: In the present study, we explored the hypothesis that initiation of PH involves the upregulation of monocyte chemoattractant protein-1 (MCP-1) in acute PTE. We evaluated the effects of resveratrol and the role of p38 mitogen-activated protein kinase (MAPK) in this process. MAIN METHODS: A rat model of acute PTE was established by infusion of an autologous blood clot into the pulmonary artery through a polyethylene catheter. Rats were randomly divided into 1, 4, and 8 hour time groups. Resveratrol, C1142 (a rodent chimeric mAb that neutralizes rat MCP-1) or SB203580 (a p38MAPK specific inhibitor) was administered to the animals beginning 1 h prior to the start of the acute PTE protocol. At each time point, the mean pulmonary artery pressure (mPAP), mRNA and protein expressions of MCP-1 were measured. The phosphorylation of p38 MAPK (p-pMAPK) was also detected. KEY FINDINGS: Acute PTE elicited significant increases in mean pulmonary artery pressure (mPAP), and up-regulated the expression of monocyte chemoattractant protein-1 (MCP-1) and phosphorylation of p38 mitogen-activated protein kinase (p-p38 MAPK). Administration of C1142 markedly reduced mPAP. Furthermore, pre-treatment of rats with resveratrol significantly reduced mPAP and down-regulated the expression of MCP-1, which was associated with robustly suppressed acute PTE-induced p-p38MAPK expression. SIGNIFICANCE: These findings suggested that MCP-1 was involved in the formation of acute PTE-induced PH, and resveratrol down-regulated the expression of MCP-1 by inhibiting acute PTE-induced p-p38MAPK activation, which contributed to the decrease in PH.